Exploration of malignant glioma infiltration factor using a blood-brain barrier model
Project/Area Number |
17K10869
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Neurosurgery
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Research Institution | Nagasaki University |
Principal Investigator |
MATSUO TAKAYUKI 長崎大学, 医歯薬学総合研究科(医学系), 教授 (00274655)
|
Co-Investigator(Kenkyū-buntansha) |
梅野 哲也 長崎大学, 医歯薬学総合研究科(医学系), 研究協力員 (00737273)
吉田 光一 長崎大学, 病院(医学系), 助教 (20393457)
氏福 健太 長崎大学, 医歯薬学総合研究科(医学系), 助教 (20437867)
馬場 史郎 長崎大学, 病院(医学系), 助教 (30530430)
鎌田 健作 長崎大学, 医歯薬学総合研究科(医学系), 客員研究員 (30549655)
|
Project Period (FY) |
2017-04-01 – 2022-03-31
|
Project Status |
Completed (Fiscal Year 2021)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | グリオーマ / 腫瘍浸潤 / 脳血液関門 / annexin / paxillin / 悪性神経膠種 / high grade glioma / anaplastic astrocytoma / glioblastoma / pericyte / tumor microenvironment / invasion / HIF1 / 悪性神経膠腫 / 浸潤能 / 脳血液関門モデル / 浸潤 / blood brain barrier / vascular endothelium / pericyto |
Outline of Final Research Achievements |
Malignant glioma is a refractory tumor with very high proliferative and infiltrative capacity. The 5-year survival rate is less than 8%. This study aimed to identify the proteins that regulate tumor infiltration, and develop therapeutic agents. We selected paxillin as a candidate for the defined protein based on the gene and protein expression analysis under ischemia in tumor cell lines on the cerebral blood barrier model. The involvement of this protein in infiltration was experimentally confirmed. Next, we examined whether the infiltration ability of the tumor was lost by suppressing paxillin. As a result, it was confirmed that the motor ability of the tumor decreased. However, statistical and histopathological studies did not confirm a significant suppression of infiltration capacity. This protein may be an essential protein involved in cell infiltration from these results.
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Academic Significance and Societal Importance of the Research Achievements |
悪性神経膠腫に対して2013年抗VEGF抗体が保険認可され、その血管新生阻害作用による抗腫瘍効果が期待されている。しかし本腫瘍が本来持つ治療抵抗性を考えた場合、血管新生阻害に伴う虚血環境に反応し、腫瘍細胞が浸潤能を高めて脳内への浸潤・転移をすることにある。腫瘍細胞の浸潤規定因子については、現在まで解明されていない。本研究では、腫瘍細胞が虚血に伴い細胞浸潤の開始行動を規定するタンパクを同定し、これを阻害する事で悪性神経膠腫治療法の開発に繋げるためのトランスレーショナルリサーチである。
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Report
(6 results)
Research Products
(4 results)